Friday, September 20, 2013

Stem Cell Treatments for Multiple Sclerosis

For patients, physicians, and researchers alike, stem cells hold the tantalizing potential of turning back the tide of multiple sclerosis, repairing damaged brains and spinal cords, and perhaps even offering something approaching a cure. There is plenty of hype surrounding stem cells, and they provide much reason for hope, but what is the reality of the current state of stem cell research for the treatment of MS?

As all patients with MS are aware, the currently available treatments do nothing to cure the disease or repair the damage that it does. At their best, today’s crop of disease modifying drugs (DMDs) quiet the disease, thereby improving the quality of life for many of the patients taking them, especially those suffering from relapsing remitting multiple sclerosis. However, many of these drugs carry with them risky side effect profiles, and though the newest compounds represent advances over their predecessors, patients are crying out for revolution, not evolution.

Stem cells could represent the revolution patients so fervently desire. Because of their ability to transform into almost any type of cell in the human body, stem cells may hold the key to achieving one of the holy grails of modern medicine, the regeneration and repair of damaged tissues. For MS patients, this could potentially mean the reversal of disability, and with it the long dreamt of disposal of wheelchairs, walkers, and canes. We are still a long way from that lofty goal, however, but the first few steps along the path to that salvation are currently being taken.

Though stem cell research is advancing in laboratories worldwide, the science of using stem cells to treat diseases in humans is still in its infancy. Because multiple sclerosis is a neurodegenerative disease, and its most prominent feature is the damage the disease does to the central nervous system, it is hoped that stem cells may hold the key to reversing the carnage wrought by the disease by facilitating the repair of damaged nerve cells. Furthermore, research has provided hints that stem cells may modulate the abnormal immune response seen in MS patients, and some researchers are even using stem cells to completely reboot the human immune system, a process that in some cases appears to stop the disease dead in its tracks.

It’s important to understand that there are two very different approaches to using stem cells in the treatment of multiple sclerosis. One approach hopes to use the cells to repair damaged nervous systems; the other uses stem cells to provide the patient with a brand-new immune system, one that theoretically will not turn against a patient’s own body. The latter approach is known as hematopoietic stem cell transplant, or HSCT, and has been used on patients in trial settings for almost two decades.

HSCT involves ablating (destroying) a patient’s existing immune system through the use of powerful chemotherapy drugs, and then intravenously infusing a patient’s own stem cells back into their body, a process depicted in the below diagram:

Once infused back into a patient’s body, the stem cells go about reconstituting their immune cells, effectively providing them with a brand-new immune system that in theory shouldn’t go to war against the patient’s own brain and spinal cord. In practice, this type of therapy has proven to be quite effective, particularly among patients with aggressive relapsing remitting disease who display a high amount of inflammation in their central nervous systems, as are evidenced by enhancing lesions seen on MRI imaging.

As you might imagine, using powerful chemotherapy drugs to destroy a patient’s immune system is not without its dangers, and early attempts at this therapy had mortality rates as high as 10%. As researchers perfected their methodology and began using less dangerous chemotherapy agents, though, the risks associated with HSCT dropped dramatically. Today, most patients undergoing HSCT are subjected to chemotherapy and immunosuppressive agents that do not completely destroy their bone marrow, and the safety profile of the procedure has improved impressively. The results achieved by this HSCT can be dramatic. In one study (click here) that looked at the long-term outcomes of HSCT, after 11 years 44% of patients who had started out with aggressive relapsing remitting disease were free from disability progression. By comparison, only 10% of those who did not display signs of active inflammation before HSCT remained stable.

One of the primary proponents of HSCT therapy for MS patients, Dr. Richard Burt of Northwestern University, stresses that the proper selection of patients is the key to the success of the treatment. In fact, the title of the paper he recently published (click here) includes the phrase “if no inflammation, no response”. “It’s the only therapy to date that has been shown to reverse neurologic deficits,” said Dr. Burt, “But you have to get the right group of patients.” In a study published by Dr. Burt in 2009, 17 out of 21 relapsing remitting patients improved after HSCT, and after three years all patients were free from progression (click here). Dr. Burt is currently heading up the HALT-MS trial for HSCT (click here). There are several centers around the world offering HSCT therapy, and there is a Worldwide HSCT Facebook group (click here) that contains information on all of the legitimate HSCT facilities worldwide. The group is populated by many folks who have undergone HSCT therapy. Be aware that it’s a private group, and you must request membership before being given access to all of the available information.

While HSCT holds much promise for putting the brakes on very aggressive relapsing remitting multiple sclerosis, it unfortunately has little to offer those with progressive disease, and does nothing to directly repair the damage done to the central nervous system by MS. Fortunately, another form of stem cell therapy proposes to do just that. Researchers in two centers in the US have received FDA approval to use bone marrow derived mesenchymal stem cells (MSCs) to repair nervous system damage, thereby possibly reversing the effects of the disease. There are additional trials using MSCs to treat MS underway internationally. Mesenchymal stem cells have the ability to transform (differentiate) into many different cell types, and could prove to be the building blocks necessary for repairing damage to the central nervous system as well as other organs and tissues. Experiments using MSCs to treat animal models of MS have been very encouraging (click here), demonstrating the cells’ abilities to modulate the immune system and spur the repair of damaged nervous system tissues. It remains to be seen whether the same effects can be achieved when using the cells to treat human beings.

The two FDA approved studies both use MSCs harvested from a patient’s own bone marrow, but employ them in very different ways. One study, currently underway at the Cleveland Clinic (click here), infuses mesenchymal stem cells intravenously into the patient, in the expectation that the cells will modulate the immune system and also initiate the regeneration of damaged tissues in the central nervous system. This study, which will eventually use MSCs to treat 24 patients, is proceeding slowly, but as the above linked to article details, one of the first patients treated is already reporting encouraging results.

The second FDA approved trial, to be conducted by the Tisch MS Research Center of New York (which just so happens to be my MS clinic), will use mesenchymal stem cells that have been transformed through a proprietary laboratory process into neural progenitor (NP) cells, injected directly into the spinal fluid (intrathecally)) of the patient (click here). Neural progenitor cells are a specialized type of stem cell specific to the nervous system that have the ability to transform into the various types of tissues damaged and destroyed by the MS disease process. Researchers at the Tisch Center have developed a way to get mesenchymal stem cells to differentiate into neural progenitor cells, and hope that by injecting these cells directly into the spinal fluid the NP cells will directly target the regenerative mechanisms of the central nervous system (click here). The stem cells themselves may act to repair damaged tissues, but they’ve also been shown to have the ability to recruit existing stem cells within the brain and spinal cord to jumpstart the body’s own repair mechanisms.

It’s important to remember that both of these studies represent a very different approach to stem cell therapy for MS than HSCT. The primary goal of HSCT is to reboot a patient’s immune system; HSCT does nothing to directly address the damage that has already been caused by the disease, but rather seeks to disrupt the disease process. Taking a different approach, the trials being conducted at the Cleveland Clinic and the Tisch MS Center seek to effect repairs on the damaged brains and spinal cords of MS patients, albeit through two different methodologies. HSCT and the reparative therapies being tested in the FDA trials have little in common other than the fact that they both use stem cells in an attempt to treat MS.

I’m sure that many patients reading this are aware that there are clinics in Central America, Asia, and Europe offering regenerative stem cell therapy to patients at hefty price tags. Some of these clinics aggressively market their services, and typically charge $20,000-$40,000 for a single round of stem cell therapy. Various Facebook pages, blogs, websites and posts on MS Internet forums extol the virtues of the treatments these clinics provide, often offering glowing testimonials from patients they have purportedly treated. Although I don’t want to disparage any patient relating their genuine experiences with these clinics, I’ve known several MSers that have traveled to a variety of these clinics and undergone stem cell treatments, and unfortunately none of them have experienced anything in the way of significant or lasting benefit.

I would caution anybody considering treatment in Panama, Costa Rica, Germany, India, or any of the other clinics offering stem cell therapy without any published scientific proof of the effectiveness of their treatments to think long and hard before committing substantial amounts of money for a therapy that, according to the experiences of people that I actually know, has very little chance of working. The two legitimate trials I outlined above both involve multiple treatments given over an extended period of time, using cells that have undergone lengthy (months long) processes of multiplication and/or differentiation in the laboratory before being transplanted back into the patient. Such regimens are not followed by the “pay to play” clinics; instead, they generally infuse stem cells back into the patient soon after they are harvested, and offer extremely limited, if any, follow-up care.

Additionally, some of these clinics don’t use a patient’s own stem cells for treatment, but rather umbilical cord cells, on which far less research has been done. The use of stem cells not derived from the patient themselves opens up all kinds of questions regarding safety and efficacy, as the cells are genetically different from the tissues they are meant to repair. If any of these clinics regularly achieved anything close to the number of successful outcomes that they claim, they would surely publish their results in legitimate scientific journals and reap the personal and professional accolades that would follow. Can you say Nobel Prize? Instead, they publish marketing materials and partner with travel agencies. Reason enough for skepticism. In short, let the buyer beware.

Stem cell therapy holds tremendous potential for the treatment of multiple sclerosis, and provides much reason for hope. The efficacy of HSCT for treating very aggressive relapsing remitting multiple sclerosis is well documented, and the safety of this treatment regimen has increased dramatically as practitioners have perfected the process. Regenerative stem cell therapy, of the type currently being trialed at the Cleveland Clinic and Tisch MS Research Center of New York, is still in its infancy, but is bursting with promise, possibly holding the key to repairing the damage done by multiple sclerosis and restoring function robbed by the disease. As with all new therapies, though, it is vitally important to not let hope eclipse reason, or let hype cloud judgment. We are at the dawn of a new age, and I fully believe that the use of stem cells will revolutionize the practice of medicine. Research into the use of stem cells to treat MS is quickly picking up steam, and in combination with other emerging therapies, rays of hope are finally being shone upon the disease and those afflicted with it. It’s about time, don’t you think?

51 comments:

Your timing is impeccable WK. I leave tomorrow for Panama. I agree that I am taking a chance. I have a statistics degree and love to play craps so I'm going to throw the dice. My hope is that I can slow the progress of my disabilities to a trickle until the holy grail of a "cure" is real and available in the states.

This is the first time I've understood exactly what the differences are in the stem cell trials being conducted as well as the procedures at the costly clinics abroad. It's great to have this synopsis. And thank goodness one of us finally put out a strong cautionary note about the heavily promoted clinics elsewhere.

I've been watching this for some time, all the while thoroughly creeped-out by the fact that some of the locations are/were also involved in CCSVI procedures, which I, myself, had done to little effect at an IRB approved study site. At least I had the satisfaction of knowing I was contributing to research and got the procedure at a reasonable cost. Oh, how we all need your big brain, Marc!

Hi Marc, thanks for breaking this down for us in a way us mere mortals can understand. When I had read about the trial at Tisch, I wondered if this was where you are treated. They said they were using existing patients for the trial - can you participate in it? I am concerned about my FB MS friends who are doing the foreign stem cell or stem cell/CCSVI treatments. I hope the best for them, but your explanation on the differences in methodology makes me think this is just another way for people to make money off desperate MS patients. That breaks my heart.

Thanks for the overview and synopsis on the Stem Cell front, Marc. Just as with the hope for CCSVI, from our anecdotal reported results, it seems to have helped very few of us so far. Still, at a certain point, after suffering for way too many years and at a certain age, one says: "I will read the literature, talk to as many people as I can and take a chance." So, I tried Tysabri despite the fact that I no longer had R/R M.S. and might have risked PML...and I tried CCSVI treatment, even though they blew through my azygous necessitating a stent placement, and I tried for it again but my internal jugular veins had all collapsed so I was no longer a candidate, and now I will travel to Panama City to The Stem Cell Institute on 10/12. My husband has been studying their protocol for months, has spoken to their docs and has found the money for it (approx. $20,000-). I have spoken to eight patients who have had this treatment done, some of whom have gone more than once beacuse of the great benefit they realized, all of whom have reported "life-changing" results. No, it is not a cure, but "reportedly" can help with incontinence, fatigue, balance, heat sensitivity, cognitive impairment, some walking, etc. Granted, these are all anecdotal reports and I know full well that The Stem Cell Institute would not be giving out names of patients for whom their treatment did not work. It is their experience that the combination of your own (autologous) stem cells derived via liposuction from your adipose tissue in combination with umbilical cord stem cells derived from the Wharton's jelly within and then grown in the lab and given back to you IV produces good results for many M.S., arthritis, spinal cord injury, C.P., autism sufferers. So, after 35 yrs of this, I figure it will not harm me, and it just might help a little. Thanks so much for the post, my dear friend.

I do not want to dampen your enthusiasm with regard to clinical trials with MSCs for MS, but you must know there is not much new in them. Clinical trials with intravenous and intrathecal injections of culture expanded MSCs were already done in several places years ago. Not accidential that these trials did not proceed into Phase 2 and 3. Their efficacy was very limited. These trials in the USA and UK just copy them. The only benefits of these trials that they give jobs to some scientists.

As for MSC-NPs, unlike neural progenitors, MSC-NPs do not yield mature neurons and glia. So, do not expect any effect similar to NPs that arise from division of neural stem cells in the brain.

Yes, you are right, lots of things are happening in the stem cell field, but potential treatments for MS are still in the phase of animal studies at best.

I do not want to dampen your enthusiasm with regard to clinical trials with MSCs for MS, but you must know there is not much new in them. Clinical trials with intravenous and intrathecal injections of culture expanded MSCs were already done in several places years ago. Not accidential that these trials did not proceed into Phase 2 and 3. Their efficacy was very limited. These trials in the USA and UK just copy them. The only benefits of these trials that they give jobs to some scientists.

As for MSC-NPs, unlike neural progenitors, MSC-NPs do not yield mature neurons and glia. So, do not expect any effect similar to NPs that arise from division of neural stem cells in the brain.

Yes, you are right, lots of things are happening in the stem cell field, but potential treatments for MS are still in the phase of animal studies at best.

I took a chance and did 18 months of Tysabri despite a positive test for JC virus antibodies. Was pleasantly surprised that it improved my heat tolerance--so what I bought for the risk wasn't just slowing the disease, it was being able to tolerate a New York summer. (I was going for two, given what summer in NYC can be like, but then moved to a milder climate on the west coast.) I'm starting tecfidera—took my first full-dose pill this morning—and so far okay on the side effects, but no idea if it's helping.

I have a relatively mild case of relapsing-remitting MS, which helps me be patient, but beyond that, I feel like I just rolled the dice, got a good result, and am not prepared to take another chance right now. They can't come up sevens forever.

Agreed. The time for stem cell therapy trials is now, the first step is always the more difficult. Dr. Goldman at Univ of Rochester is conducting trial associated with New York State Stem Cell Board. Also, California has strong R&D in stem cell biology, especially UC Irvine and Gladstone Institute in San Fran., home of Dr. Yamanaka who did pioneering work on stem cell differentiation earning Nobel prize.

I am wondering myself if stem cells will do anything for multiple sclerosis. :-) Has everyone seen this link, below? No doctor will give me the three antibiotics, but I am trying. Good luck, my friends. :-)http://www.youtube.com/watch?v=EpMvDe8-qsMhttp://brokenartgallery.com/

I do not find myself feeling particularly hopeful at all. There was NO treatment for primary progressive MS when I was diagnosed over four years ago and still there is absolutely nothing. All I do is help a neurologist take home $ 13,000 a month in income, while I barely survive financially in a very low paying field and have a $ 5,000 per year health care deductable that does not even include my $ 50 doctor visit co-pays or any meds. I can no longer do most of the fun things that I used to do. I'm like a different person now. It might be easier to remain hopeful when you are not steadily losing your ability to physically function and go to docs who know absolutely nothing about your disease, even though they subspecialize in it. I am facing a future of total poverty because of PPMS and not being married most likely a nursing home as well. You try to make the best of each day and enjoy life as best you can despite everything, but having much hope does not really fit into the equation, unless paralysis is a good thing for us, I have thogh decided to get much less health care in general and instead blow money on travel so that it does not all go to Medicaid spend down when i can't work. That is the one positive about MS, going downhill farly rapidly means doing some things NOW, while it is still possible, even though it has become a lot more difficult. Sorry for the downer vent everyone, but yes it would be nice to have SOMETHING for us too. I would think twice befroe taveling for stem cells. It's certainly a huge money maker, same with the CCSVI treatment. As always, thanks for your writing Marc. You are always much more upbeat than I ever feel living with this horrid scourge.

Same here. I too am single and diagnosed with PPMS in 2008. Im now very close to needing a wheelchair full time. Licing in a nursing home is a very likely probability in my future as well. Doctors are a joke. They have no idea what to do for our MS subgroup and as much as admit it! My personal opinion is that until medicine/physicians can offer viable treatments they have no have no right to discourage patient from seeking alternatives.

i recently had a stem cell transplant at northwestern and it was amazing! have had ms for 13 years and almost no physical problems, mostly cognitive. the past year i was using a walker, then wheelchair. after northwestern i'm using a cane, no more pain, more energy. i'm amazed and at the same time infuriated with the drug companies - steroids don't work anymore and my risk of pml is too hight for tysabri. everyone blew me off - we went to chicago and i am getting my life back.

I was part of the stem cell study at the Cleveland Clinic (#19 of the 24). This Phase One study (sponsored by the Department of Defense) was to prove to the FDA the safety of the procedure.From what I was told, none of the participants had any bad reactions.Though I did not experience any benefit, I still believe stem cell therapy is the future of medicine.

My mother just had a stem cell procedure done at Stemgenex for her MS and she's doing absolutely amazing. They used an iv administration along with injections to the base of her spine for her drop foot, injections to her bladder for her incontinence and most importantly intranasal administration of the stem cells to her brain. She responded very well to the treatments and we are so thankful the we decided to explore stem cells for her disease. We really had our doubts but we are so thankful we decided to try it.

With stem cell doctors hope to win about 300 different diseases. But so far it is only a desire, and present positive results even a little about what they say. After all, no one knows how to behave like stem cells in the body, say, 5 years. While stem cell therapy is the only clinical trial.

Hi Marc:Thank you for calling attention to a much needed treatment for those with MS and I don't just mean for the RRMS patients, no offense but I think they have enough drugs on the market for them already. The MS society donates money for research but fails to require that it be used to research treatments for all forms of MS. Once again leaving others with no hope.I have PPMS, diagnosed in 2011 and was told there is no treatment for me. I live on pain pills and anti anxiety medicine. In 2012 I was diagnosed with Breast Cancer and because of one of the chemo drugs I am no eligible for any clinical trials, yet no one will answer why. One study told me that they would not enroll me due to the Cytoxan but that when the drug hits the market that I could take it..... why would I, if it was so dangerous that I couldn't be a part of the trial wouldn't it be just as dangerous? In 2013 after complaining for several years and having proof from my PET scan that my thyroid gland was dying - I finally found a doctor to listen and was diagnosed with Hashimotos Thyroid disease but not before I totally lost my sense of smell that will most likely never return. Stem cell treatments could fix all of this but the USA is far too greedy to cure anything. The Myelin Foundation is talking about treatment for re-myelination in 2019. I will be so old by then that it won't make much of a difference. MS will and has stolen every ounce of quality of life I had.

I am going for stem cell tx next week at Stemgenex. I can only pray for benefits from this experimental tx. I have progressive RR MS. I feel I have nothing to lose and it is local and affordable. I wil let you lnow my results.

I don't fully agree with your assessment for HSCT. Although Dr. Burt does not treat anyone with any progressive form of MS, he is the only one in the world that chooses to do so. Germany, Russia (where I'll be treated this summer), Israel, S. Africa, India, etc. all treat all evolutionary forms of MS. As a matter of fact Dr. Burt's initial studies contradict his current position on this issue. For any progressive patients, the EDSS alone was the biggest predictor of success. If you are SPMS with <6.0, you have anywhere from 70-80% chance of halting progression for five years. The above study you reference with 44% PFS was early HSCT with total body irradiation and busulphan, two very dangerous chemo protocols that contribute to progression, esp. in high EDSS patients, and have since been abandoned by low intensity lymphoablative protocols, much safer with lesser mortality.

According to the majority of the literature I've read, when it comes to progressive MS the greatest predictor of HSCT efficacy is the presence of active inflammation, i.e. enhancing lesions on an MRI. While these are fairly common in folks with early SPMS, one of the distinguishing characteristics of PPMS is usually the decided lack of enhancing lesions. I'd certainly advise those with progressive MS who have enhancing lesions to at least consider HSCT, but I'm dubious as to whether those without enhancing lesions stand much of a chance of benefiting from the procedure. I believe EDSS is actually secondary to the presence of active inflammation, but one could postulate that those progressive patients with more advanced disability most likely will not show signs of active inflammation, as they quite likely would have left the active stage behind, unfortunately.

Marc, thanks for responding so promptly. Overall, yes, the success based on MRI parameters of inflammation and stability favors active inflammation, such as is mainly seen with RRMS. However, a broader review of the literature shows a more mixed picture. Studies by Shevchenko et. al (Moscow) showed that the overall progression free survival of 52 SPMS patients without active inflammation as measured on MRI, was 72% at 48 months. Granted, that's nowhere near a "cure", but there is no other medication/therapy that comes close. In another earlier study by one of the pioneers, Fassas, in 2002 reviewing a varied EBMT database of multicenter trials, 66% of PPMS progression free survival and 78% of SPMS PFS was found at three years. Long term follow up still needs to be determined, but the fact that it has an effect on PPMS is interesting. According to Barth's School of London, PPMS still manifests with inflammation at the cellular level and as you know, MRI gross indicators of inflammation such as definite Gd-enhancing lesions do not correlate well with progression or pathology. That Tcells are still being trapped in the CNS, auto reactive as they are continuing to damage axons, is consistent with both SPMS and PPMS. As a matter of fact, this may describe why Tysabri may have a positive effect on SPMS (currently being studied with the ASCEND trial) that has shown reduced markers of axonal degeneration and increased remyelination. Therefore, Dr. Burt may be the only clinician that demands refractory RRMS w/active inflammation for his study trial (which has a different design that is specific for that trial); other international centers also treat progressive MS: Heidelberg, China, Moscow, Israel, etc. I think it's oversimplifying to state that only active inflammatory disease is halted by HSCT. The many centers' experience and prospective studies tell a different story. The fact that HSCT doesn't "work" on progressive patients also contradicts the evidence that cyclophosphamide as a stand alone drug slows SPMS progression by 65%+ in the latest trial. Also, Rituximab is being studied for SPMS and all indications are that it should be successful. Will these antibodies or chemo agents completely halt MS? Even if they don't, that still makes them more effective than a lifetime of DMD's that have been shown to have NO effect in disease progression and high risks for side effects, especially Tysabri with not just PML, but CNS Lymphoma, melanoma, meningitis, etc. One last point about HSCT an progressive MS: PPMS is definitely the least amenable to treatment because primarily, it is an axonal pathology. But is it really certain that axons, which have been known to survive demyelinated for a long time, all reach some threshold after, say, ten years all degenerate completely where there is no autoimmune component? Yes, I do agree more longer term studies for HSCT's effectiveness for all MS subtypes need to be done. But prospective and retrospective studies, now fifteen plus years, show that effectiveness, primarily in SPMS,( although not as high as early RRMS) is still impressive at five years.

Thanks for all of the info. PPMS is definitely hard to crack beast, in the opinion of some researchers it may even be a different disease entirely.

Just a couple of points: in regards to cyclophosphamide, the HyCy treatment, previously called Revimmune, was not shown to be effective on patients without active inflammation, as far as all the results that I've come across indicate. In fact, when the revimmune project was first started at Johns Hopkins, I applied for the treatment, but was rejected precisely because I don't exhibit any signs of active inflammation. I know a few patients who underwent the treatment who had SPMS, and few if any saw lasting benefit.

Rituxan as a treatment for PPMS failed trials about four or five years ago, although a subset of patients on whom the drug may have been effective was identified. Rituxan therapy will not be a one and done treatment, either. Patients will be required to stay on the drug until something better comes along. It's a long acting drug, though, so infusions every six months will be the most likely treatment schedule. There are currently several newer versions of Rituxan in trials, because Rituxan will soon be an off patent drug, so no profits for Big Pharma. There is some conjecture that the drug works because it destroys B cells, which harbor EBV in the human body.

Lemtrada (previously called Campath) is another monoclonal antibody shown to be extremely effective in treating inflammatory forms of MS. Although it was just rejected by the FDA, it's been approved almost everywhere else in the world. This drug is an induction therapy, in that after an initial course of treatment (over a one-year period) patients shouldn't require additional infusions. This drug works much the same way as HSCT, only in a slower fashion. It gradually wipes out a patient's immune system, giving the body a chance to reconstitute a "new" one. Recent studies done comparing Lemtrada to the interferons showed the drug to have a startling rate of effectiveness, over 50% of RRMS patients treated with it show no evidence of disease activity five years after their last treatment. In patients without active inflammation, though, the drug has not proven to be effective. Also worth noting is that the drug has a very serious side effect profile, which includes autoimmune thyroid disease and a potentially fatal autoimmune blood disorder. Patients need to be monitored for these conditions for the rest of their lives after being treated with Lemtrada.

As you say, this MS presents very complicated picture, and the progressive forms of the disease are still largely beyond understanding. Don't forget, it still only an assumption that MS is an autoimmune disease. Certainly, the immune system plays a large role in the disease etiology, but the aberrant immune response is likely a symptom of some greater ill. It is entirely possible that immunoablative therapies work because they are inadvertently wiping out an as yet undiscovered MS triggering antigen along with the immune system. As I mentioned, B cells harbor EBV, which is highly suspected as being one of the primary culprits in triggering the disease. EBV has been shown to activate HERVs, which could lie at the Genesis of not only many "autoimmune" diseases, but also cancers and some mental illnesses.

All interesting stuff, but all unproven. I wish you the greatest success with your treatment, and I would encourage any patient with signs of active inflammation to thoroughly investigate this type of therapy. However, if I were a patient without highly active disease, I would proceed with the utmost caution. HSCT is not without its dangers and is a rough process to go through, so very careful risk/reward calculations must be thoroughly considered.

Regarding my above comments about Rituxan: the mechanism of the drug is the destruction of B cells, so its effectiveness in treating MS is obviously due to that action. Didn't mean to imply that destroying B cells was a side effect of Rituxan treatment, in fact it is the drugs mode of action. However, it could be that it works on MS not because of B cell destruction per se, but rather that those cells harbor EBV, which has been shown to be present in 100% of MS patients. This is not a widely accepted theory, but has been proposed by some researchers. It's interesting to note, also, that up until a few years ago it was thought that MS was a strictly T cell mediated disease. The success of Rituxan in RRMS took many by surprise.

Thank you again for your response. I agree completely with better outcomes for early/inflammatory MS. And that secondarily, perhaps, EDSS score plays an important role in transplant's success in progressive disease. But the international center wide experience so far has been positive for early SPMS as well, inflammatory and non-inflammatory. Interestingly, the better outcomes with SPMS , Russia and China, are also the ones that don't use ATG/CD-34+ depletion but instead use Rituximab which as you mentioned, affects B cells. Again, conjecture. I am early non-inflammatory SPMS on Tysabri for three years; to illustrate the difficulty in "diagnosing" the different aspects of MS, my neurologist thinks I'm still RRMS but that the lack of lesion load is due to Tysabri. I've read a lot about HSCT and SPMS over the last year and have come to the conclusion that although efficacy is not as robust as in active RRMS, the figure of 72-75% PFS from different centers has me convinced that the consistency may not be random chance. Even though proper RCT's have not been done yet, both prospective studies and meta analysis of existing studies going back to 2002 or so, show similar such percentages. The other observation for me that was the clincher is that mitoxantrone is very effictive in SPMS, relapsing or otherwise. So here we have, along with cyclophasphamide, two stand alone chemo drugs that appear to be somewhat effective in SPMS. I am aware as you mentioned, that Hi Cy (Cyrevia) and lemtrada both had minimal, if any effect on progressive disease. But what was the EDSS for patients studied? Again, I'm starting to think that some threshold is reached when EDSS reaches, say, >6.0 whereby disability progresses relentlessly. I also think, though, that there must still be some low-grade inflammation occurring in both SPMS and PPMS without showing as gross Gd lesions on MRI. It cannot be that axons are just being transected by an as-yet misunderstood mechanism. But then, I could be wrong. The research does show that there is still inflammation in progressive disease, although not as pronounced. Perhaps this explains some evidence for even SPMS being slowed down early enough? (I do understand that stopping progression is still elusive. Even RRMS has only been followed up for durability up to ten years. What happens after is still a mystery). As for me Marc, even if I get two or three years out of it, there is much in HSCT literature showing the potential benefits of add-on treatment if relapse, such as Cy and Mitoxantrone, to further silence active disease. Just my thoughts and I welcome yours

I think we are in basic agreement. The fact that you've been on Tysabri for three years certainly impacts any indicators regarding your progressing from RRMS to SPMS, and also very likely explains your lack of enhancing lesions. The latest figures on patients using Tysabri show that a significant percentage of them showed no evidence of disease activity (NEDA) while on the drug (meaning no enhancing lesions, no relapses, little if any progression). It's a powerful drug, not without its downsides, of course, but proving to be perhaps even more effective than was initially expected.

As for the relationship between EDSS and active inflammation, I think concentrating on one over the other is misguided. People with higher EDSS scores would quite likely have had the disease for a longer duration, and thus would also very likely be more prone to being passed the active inflammatory stages of the disease. One wouldn't expect most patients with an EDSS over six to display much if any active inflammation.

I think it's beyond doubt that there is a neurodegenerative process underlying the disease that has little if anything to do with inflammation. Certainly, the Laquinimod trials point in that direction; the drug showed little influence on relapses or enhancing lesions, yet when the results were looked at more closely Laquinimod did appear to have a positive effect on the inhibition of progression. Also, clearly, folks with PPMS, who generally start out with noninflammatory disease, suffer severe neurodegeneration despite that lack of inflammation. Yes, there is probably inflammation present at subclinical levels, but it's becoming increasingly apparent that inflammation is only a very obvious and easy to measure aspect of the disease, making it ideal for use as a clinical trial biomarker, but one that may present researchers with a less than complete picture of the disease, or any particular compound's ultimate efficacy in treating the disease's long-term ramifications.

Given the little I know of your disease history, it does sound like you stand a very good chance of experiencing significant benefit from HSCT. I certainly wish you many years of NEDA, and I hope for you the procedure does turn out to be a cure, or something close to it. Be careful when promoting HSCT, though, especially to those who likely don't stand a great chance of benefiting from this still radical procedure, as it's my belief that false hope is worse than no hope at all, especially when large sums of money and the potential for physical complications are involved.

Hi Marc. My disease history is 13 years diagnosed in 2001, but probably had it sooner due to some "phantom" tingling in my fingers. At the time, I thought it was a sports injury. I agree completely with your assessment of Tysabri; unlike some others, I was never really scared of this medication as it is right now, at least for RRMS, the gold standard. I have been on it three years and now, being JC+, am getting a little concerned. An article just posted that the latest PML figures are 1/75 patients. That's about 1.3% and PML, if it doesn't kill you, will likely leave you with severe disability. Which puts the risk of mortality of 1% with HSCT into perspective. And, i tis only a one time treatment whereas the risks of very long term Tysabri use are just now being elucidated. At any rate, I have no enhancing lesions, so natalizumab has been good to me. Truth be told, if there was no risk, I would take it indefinitely because I have read a lot about its effectiveness and chances are, it will soon be indicated for SPMS, too. Already promising results have come out of the ASCEND trial. Now, I am educated in biology and am anything but desperate to believe in "cures" (note the CCSVI scam). And I am a member of a HSCT forum on FB. Many people on this forum have no clue, sadly, of the advantage and risks of HSCT. Many in wheelchairs, EDSS 8.0 or above, erroneously believe that it will reverse their disability. The enthusiasm can at times be likened to the CCSVI placebo effect. There are, for example, people on the forum that have been treated with PPMS that think they are doing "better" when in actuality, they have been back home for just three months and, as we both know, will likely progress at some time point. And the Moscow clinic makes no promises: they spell out their outcomes which mirror their peer-reviewed summaries in the literature and refuse to treat PPMS or SPMS with a EDSS of 4.0 or above. They understand that not only will there be little to no effect, but there is a risk of further progression. Dr. Fedorenko and Shevchenko of Maximov clinic is currently merging their expertise with Israel's clinic and one of the pioneers of lymphoablative HSCT: Dr. Slavin. I have the confidence that much of the research out there does show a positive effect on early SPMS with lower EDSS. Again, not a cure. More than six years? No one knows. But then again, even in inflammatory RRMS disease, fifteen years only showed 44% PFS with Fassas' landmark review. Therefore, I 'm not going into this thinking I'll never need another med again. BTW, there is very hopeful research being done with Dr. Kerr at Mayo Clinic who has advanced the regrowth and wiring of lost axons in mice to essentially almost "cure' paralysis. He thinks, 15 years? It gives anyone in a wheelchair much hope. And even people like me with foot drop and a weak leg, hope. There's a lot to look forward to Marc. I recall one 19 year old girl who saw Dr. Kerr (who specializes in Transverse Myelitis, but is obviously very relevant to MS) and asked him the question if she would ever be able to walk again. His response: You will not be an older woman in a wheelchair. You're likely familiar with him. Thanks again for your input

Thank you for all of your input, Spiro. You're a fine example of an educated patient to is his own best advocate. It's my fervent wish that more patients would take this approach, but unfortunately much of the medical nomenclature is specifically designed to confuse laymen and keep the forbidden fruit of knowledge shared by only those with degrees in medicine. Truth is that much of what is published isn't really all that complicated, only phrased using complicated terms.

If I were in your position, I'd probably be making the exact same choices you are. I'm sure you are up on all of the latest info regarding JC virus antibody titers and their relationship to PML risk in those taking Tysabri, which I presume is how you came up with your one in 75 figure. Very happy that the drug has been so good to you, but you have approached the point where the risk/reward ratio is tilting too far towards "risk".

I wouldn't be so quick to call CCSVI a scam, per se, but hype did eclipse any realistic expectations for the theory or the procedure used to correct it. I know several patients who do seem to have benefited from CCSVI venoplasty, but many more who saw little or no legitimate benefit. Much research still needs to be done, as I think that there is some vascular component to the disease, and perhaps other neurologic diseases. I only hope the baby isn't being thrown out with the bathwater as researchers and patients both seem to be turning their backs on CCSVI in large numbers.

You've certainly done your research regarding HSCT, and given your disease history, it would appear that you are very good candidate for the procedure. I wish you nothing but the absolute best, and would appreciate it if you let me know how things go. You can always email me at WheelchairKamikaze@Gmail.com. Hope I'm not making too much of a leap, but I'm assuming that you are Greek, and would love to hear that several months after the procedure you are ecstatically breaking dishes and downing ouzo.

As for regenerative therapies, yes, I am quite optimistic. Unfortunately, my disease is progressing at an alarming rate, so sooner rather than later would suit me just fine. I am familiar with the work of Dr. Kerr, as well as several other researchers who are hard at work on neuroprotective/regenerative strategies. May the wisdom of the universe lend them a hand…

Thank you ! I was just diagnosed and I honestly have no clue what i am dealing with.. I have weak leg , and God help us all there will be a cure soon ! I need someone to talk my neurologist is not very good at explaining.. I do my education about this online .. So there are hopes and there's reality .. If you have a chance and time my fb is eva marinova...

Marc, again, I appreciate your input and kind words. If HSCT doesn't work for me, I won't be devastated. I'm going into this expecting possibly some short to medium term relief of progression. If I progress sooner, then so be it. No regrets. I like your comment about Laquinimod. There is a similar neuroprotective compound for both PPMS and SPMS called MIS-416 in phase I trials from New Zealand. It's a proprietary molecule by Innovative Immunotherapeutics (I believe that's the name); they presented at ECTRIMS last year and secured Phase I monies. In five years, hopefully, it'll profoundly prevent further progression, as it has been shown to do in mice. In addition, while we're both waiting, check out MitoQ, a mitochondrial targeted CoEQ capsule that has been studied in mice and has shown slowing/halting progression of axonal loss and even reversal of some parameters of neurodegeneration. It's being studied (see listing in PubMed) for over ten years. Recently, as you are well aware of, statins for progressive disease are being studied and may be fast tracked if they can overcome funding. Then, there are studies for alpha lipoic acid and other antioxidants which prevent degeneration, green tea, etc. And, I didn't mean to dismiss CCSVI out of hand, so I apologize. I try not to preach as I obviously don't have all the answers (or maybe any answers). I believe the latest review I read on the procedure was in Lancet and I thought of it as the last nail in the coffin. There may very well be a vascular component to MS, perhaps tied to permeability of the endothelium, etc. But so far, the evidence for occlusion of cervical vessels associated just with MS patients is weak at best; however I remain open to it. And you are correct, I am Greek (nice Irish name, eh?). I gotta say, your blog is immensely educational. It's an excellent overview of many aspect of MS treatments, topics, etc. It's a tremendous service to all MSers.. I had been reading this site for awhile when I returned to it to read your overview of HSCT. And pretty much, you are spot on . It took me a year to collate all the info and peer-reviewed literature to convince me that it may even be effective for progressive MS. I didn't want to drink the Kool-Aid on the facebook forum, so I read and stayed on the sidelines. Realizing that much of what's on there are patient testimonials/anecdotal evidence, I needed statistics to back up any assertions. Again, RRMS was a no-brainer. SPMS, not so much. I scheduled in August, but five months away for a skeptic like me can mean I may still pull the plug. Who knows?

Has anyone with PPMS gone to Stem Cell Treatment Institiue in Tijuana? They claim to have a 88% cure rate using both forms of stem cells (your own and a donor's). The US is sorely behind in it's research - other countries are much further along leading me to have more faith in it's clinics.

Hello everyone and thank you for sharing your finding ! I was recently diagnosed its been two weeks of thaking copaxon , i try to read and educat my self as much as i can , and like all of us i pry for a cure ... Hopefully soon ! I read a lot about step cells but this article was the most helpful and realistic... I have a question now is awmost 2016 and i guess the medical fild has evolved... I was told about new medication once a year Lemtrada ? What do you think , and what about medical marihuana? My fb is eva marinova pls contact me i will be extremely thankful ! Happy holydas to evryone !

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Regretfully, due to the high volume of e-mail received and the realities of living with progressive MS, I'll no longer be able to respond to all e-mails sent. I do read each note, and will do my best to answer as many messages as I can.

About Me

I'm Marc, a 53-year-old male, living in New York City with my lovely and wonderful wife Karen. Diagnosed with Primary Progressive Multiple Sclerosis in March of 2003, I now require a wheelchair to get around the city. I like to drive the wheelchair at full speed, thus the moniker "Wheelchair Kamikaze". I've managed to rig a camera to my chair, so I'm able to take videos and still photos from the unique vantage point of a wheelchair, which I intend to post here.
Before getting sick, I was the Director of DVD Production for one of the major international music companies. Yes, I was once a member of the Evil Empire...
Prior to my enlistment in the Evil Empire, I worked as a video producer and editor.
I grew up in New York City, and spent the 1980s in Boston (college and postcollege rock 'n roll craziness). During the 1990s, I lived in South Florida, until I woke up one morning and realized I was living in South Florida, came to my senses, and moved back to New York.
I hope you like my blog...